The Flu Pandemic

By Robin Marantz Henig;

Published: November 29, 1992

During the flu epidemic of 1918, according to medical lore, victims were struck down almost in midstride. Four women in a bridge group played cards together until 11 o'clock in the evening. By the next morning three of them were dead. One man got on a streetcar feeling well enough to go to work, rode six blocks and died. During the single month of October, influenza killed 196,000 people in this country -- more than twice as many as would die of AIDS during the first 10 years of that epidemic. By the end of the winter of 1918-19, two billion people around the world had come down with influenza, and between 20 million and 40 million had died.

The flu outbreak of 1918 was "the most devastating epidemic that we have ever had in history," says John R. La Montagne, chief of infectious diseases at the National Institute of Allergy and Infectious Diseases in Bethesda, Md. "And it happened in this century. No one really knows why it occurred, but there's every expectation that if it occurred once, it can occur again." The 1918 influenza pandemic killed as many people in a single year as died in the four-year Black Death, the bubonic plague that ravaged Europe from 1347 to 1351.

We like to believe such plunder is an ancient relic; whatever was killing people so ruthlessly in 1918 must be something we can treat by now. Modern medicine has given us an influenza vaccine, an anti-influenza drug (amantadine) and plenty of antibiotics to prevent or treat secondary bacterial infections. But in the face of a virus that kills so rapidly, all the antiviral drugs in the physician's armamentarium would be impotent. If a strain similar to the 1918 variant were to emerge today -- a strain that, last time around, killed literally overnight -- some experts believe that even modern medicine would be helpless to prevent many related deaths.

THE EXISTENCE OF the influenza vaccine -- not to mention that pervasive phrase "just the flu," conveying as it does a certain harmless inevitability -- may give us a sense of false security when it comes to the possibility of a pandemic outbreak of influenza. (A pandemic is an international epidemic, with disease occurring at a higher-than-expected rate on several continents at once.) In fact, the flu vaccine must be reformulated each year to keep pace with the newest variants of this fast-mutating virus, and in the case of an unanticipated outbreak it would take so long to manufacture and distribute an appropriate vaccine that thousands might die waiting.

More stable viruses, like smallpox and polio, are relatively easy to control with an effective one-time vaccine. Not influenza. Because the virus mutates so frequently, the flu vaccine must be concocted anew each year, based on scientists' best guess of what surface proteins will determine the nature of the next season's outbreak. Once they forecast the probable composition of the virus, scientists choose the appropriate antigens to make their vaccine. They must know by mid-February of any year which antigens to include in the following winter's formulations, if they hope to insure production of adequate amounts of vaccine for delivery by the start of the flu season in December.

In developing a flu vaccine, researchers have managed (so far) to outsmart their foe. They have succeeded by turning the virus's own best weapon against it. Unlike almost all other emerging viruses -- viruses, like the one that causes AIDS, that turn up in a new species or in a new geographic location (box, page 55) -- the influenza virus has mastered and become dependent on just one terrific trick: the speed with which it evolves. The laboratory strains developed for the influenza vaccine, the ones that can stop an epidemic in its tracks, have capitalized on the virus's notorious ability to recombine. But it is this very trait that makes any vaccine against this fast-mutating virus so frustratingly short-lived.

The recipe for making the flu vaccine is simple. Take the current year's variant of the influenza virus, throw it into a stew with a strain of virus that leads to rapid proliferation (a strain known as PR-8) and let the virus do what it does best: incorporate the fast-growing strain into its own genes and start replicating it. From there, it's an easy matter to take those plentiful viruses and attenuate them for a flu vaccine.

But the scientists who must determine what virus will cause the next year's illness run a high chance of being wrong. Some observers have put the odds of success at no better than 50-50. Even when they are right, the vaccine lasts only as long as that year's strain. By the next flu season, the fickle virus is almost certain to be wearing a new protein coat, a disguise sufficient to slip right past whatever antibodies were formed in response to the previous year's shot.

BECAUSE MUTATION IS SUCH A crucial factor in the virus's reproductive strategy, any discussion of influenza must include a discussion of how the virus itself changes from one strain to the next. The mutations that lead to major changes in viral surface antigens -- changes that create the pandemic strains of influenza -- are quite rare. Pandemic strains have occurred just three times in this century: in 1918, the year of the so-called Spanish flu; in 1957, when a new strain called the Asian flu emerged, and in 1968, when a third strain was introduced, known as the Hong Kong flu.

Robin Marantz Henig is the author of "A Dancing Matrix: Voyages Along the Viral Frontier," from which this article is adapted. The book will be published in February by Alfred A. Knopf Inc. Copyright $; 1992 by Robin Marantz Henig.